Define the term gastrointestinal stromal tumor.
malignant mesenchymal neoplasm of the gastrointestinal tract that arises from interstitial cells of Cajal or precursor cells
When is the typical age of onset?
∼ 60 years of age
With which mutations is the GIST associated?
associated with c-KIT gene mutations and PDGFRA gene mutations
Describe the pathophysiology of mutations in c-KIT or PDGFRA.
mutations in c-KIT or PDGFRA → phosphorylation of receptor tyrosine kinases → perpetuatal, ligand-independent activation of downstream effectors → ↓ apoptosis and ↑ cellular proliferation → neoplasia
Where are GIST mostly located?
Stomach (60%)
Small intestine (35%, more frequent in familial forms and syndromes)
Colon, rectum, esophagus, or omentum (5%)
Describe the clinical features.
Small tumors (< 2 cm): often asymptomatic
Large tumors (> 2 cm)
Ulceration, bleeding → anemia, melena, and hematemesis
Obstruction → ileus
Describe the diagnostic tests.
Imaging: CT, MRI, ultrasound
Endoscopy with biopsy
Immunohistochemistry
Molecular genetic testing: c-KIT or PDGFRA mutations
Describe the general treatment.
Treatment involves surgical removal and treatment with tyrosine kinase inhibitors such as imatinib or dasatinib.
How are small GIST treated?
Stomach: to be observed; endoscopic removal possible
Other localization: resection
How are large GIST treated?
Surgical excision is required.
Neoadjuvant and/or adjuvant treatment with imatinib may be considered.
How are nonresectable/metastatic GIST treated?
Palliative treatment using imatinib
In the case of imatinib resistance, the second-line treatment is sunitinib.
Elaborate on the prognosis.
Depends predominantly on tumor size, mitotic rate, and tumor location
Small tumors (> 2 cm but ≤ 5 cm) and gastric location are associated with a low risk of disease progression, metastases, and recurrence (2%).
However, large tumors (> 10 cm), tumors > 5 cm with a mitotic count higher than 5/50 HPF, and jejunal/ileal location carry a significantly increased risk of progression (90%).
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